In baseball this is the part of an individual's swinging range in which as a hitter they can make the best contact with the ball. If a pitch is right in your wheelhouse it is right where you want it, in the spot where you have the best chance of hitting it well.

The term is also often used to explain something that falls into a person's area of expertise.

ESPN: "Konerko can hit the ball 500 ft. if it's pitched right in his wheelhouse."

Child 1: "How can we get this hot girl to take her clothes off?"
Child 2: "Ask Hugh Heffner, that's right in his wheelhouse."

Anything that can be acted on with confident success.
I'm guessing it originates from the fact that a wheelhouse is the room on the bridge of a ship where you steer from, providing you with clear view & control to steer the situation.

Have the handsome guy address that roomful of female sales potentials; it's right in his wheelhouse.

A two-ton, four-wheeled, enclosed (as in a house) vehicle used by the majority of Americans for their daily transportation needs. While technically operated in the public right-of-way, Americans consider the interior of the wheelhouse to be their own, exclusive space, where they are not expected to socialize with their fellow citizens (similar to the non-wheeled house where people typically sleep at night).

It's no wonder the average American feels no sense of civic responsibility: Their lives consist of going from their house, to their wheelhouse, to work, and back.